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Zeno Bisoffi

WHO Collaborating Center on strongyloidiasis and other

i t ti l iti i f ti

ICMH, Rome 2018Symposium, 3rd  October 2018

Parasites: Malaria, Chagas, Schistosomiasis, and Strongyloidiasis

Strongyloidiasis and schistosomiasis: screen, treat or forget?

Global distribution of schistosomiasisSchistosomiasis:Important health problem?

Adapted from Colley, Lancet 2014

>260 million infected. ~ 85% (over 200 million, 280.000 deaths) in sub-Saharian Africa

Some 30–100 million people are estimated to be infected

worldwide(probably an underestimate)

At least370 

millionpeople infected

Bisoffi Z, Buonfrate D, Montresor A, Requena‐Méndez A, et al. (2013) Strongyloides stercoralis: A Plea for Action. PLoS Negl Trop Dis 7(5): e2214. doi:10.1371/journal.pntd.0002214http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0002214

StrongyloidiasisImportant health problem?

Buonfrate Dora, Gobbi Federico, Marchese Valentina, Postiglione Chiara, Badona Monteiro Geraldo, Giorli Giovanni, Napoletano Giuseppina, Bisoffi Zeno. Extended screening for infectious diseases among newly arrived asylum seekers from Africa and Asia, Verona province, Italy, April 2014 to June 2015. Euro Surveill. 2018;23(16):pii=17-00527. https://doi.org/10.2807/1560-7917.ES.2018.23.16.17-00527

Important health problems in migrants?

Important health problems in migrants?

Schistosomiasis: pooledprevalence >20% SSA

C. Greenaway et al. 2018. Prevalence of strongyloidiasis and schistosomiasis among migrants (Lancet GH, under review)

24.1%

Accepted! Great job Chris!!!

Important health problems in migrants?

C. Greenaway et al. 2018. Prevalence of strongyloidiasis and schistosomiasis among migrants (Lancet GH, accepted)

Strongyloidiasis: pooledprevalence >10% EAP, SSA and LAC

17.4% 11.4%14.3%

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Important health problems in migrants?

Rome 2018, preliminary, unpublished data:

Strongyloidiasis prevalence (IFAT): SSA 81/398 (20%)LAC 37/248 (15%)

Schistosomiasis prevalence (ICT): SSA 66/400 (16.5%)

L. Marrone et al., September 2018

Cicle of S. stercoralis

Buonfrate D, Perandin F, Formenti F, Bisoffi Z. Novel approaches to the diagnosis of Strongyloides stercoralis infection. Clin Microbiol Infect. 2015 Jun;21(6):543-552.

ABDOMINAL PAIN

DIARRHEA

F. Tamarozzi et al., TMIH 2018, under review

Symptoms of chronic, uncomplicated strongyloidiasis

ITCHING

URTICARIASymptoms of chronic, uncomplicated strongyloidiasis

Anemia? Stunting? Other?

F. Tamarozzi et al., TMIH 2018, under review

Immune depression

hyperinfection ‐ dissemination

(accelerated autoinfection)  (to ) 

Fatality rate: 50‐86%

X

Buonfrate D et al. BMC Infectious Diseases 2013 13(1):78

Severe strongyloidiasis: 67% patients under steroids

Buonfrate D et al. BMC Infectious Diseases 2013 13(1):78

Other conditionsHTLV 1HIV AlcoholismMalnutritionPregnancy?TransplantCancer

How to quantify the risk ofhyperinfection/dissemination? We

need a stroke of genius!

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Test Prevalence PPV NPV

BORDIER ELISA 10,0% 85.4% 98.8%

20,0% 92.9% 97.4%

IVD ELISA 10,0% 91.8% 99.0%

20,0% 96.2% 97.8%

Diagnosis: is a satisfactory test available for screening?

Bisoffi Z, Buonfrate D, Sequi M, Mejia R, Cimino RO, Krolewiecki AJ, et al. (2014) Diagnostic Accuracy of Five Serologic Tests forStrongyloides stercoralis Infection. PLoS Negl Trop Dis 8(1): e2640. https://doi.org/10.1371/journal.pntd.0002640

Is an effective treatment available? Ok ivermectin…But howmany doses?

Preliminary results…

WHO Collaborating Center on strongyloidiasis and other intestinal

parasitic infections

No difference!!

Schistosomiasis ‐ Lifecycle

Adapted from Colley, Lancet, 2014 16

Schistosoma in the mesenteric veins

Source o cambiare

Schistosomiasis• S. mansoni (japonicum): mild to moderate (if any) intestinal symptoms for years;• Liver fibrosis, portalhypertension, death ifuntreated

• S. haematobium: mild tomoderate (if any) urogenitalsymptoms for years;• Hydronephrosis, renal failure, class A carcinogen for bladdercancer

Important health problem?

Source: F. Tamarozzi, CTD Negrar

Important health problem?

This bladder “tumor” virtually disappeared in one month after pzqtreatment

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Gobbi F et al. Lancet Inf Dis 2017

New insights: schistosomiasis and the lungs

Patient 6

Patient 7

90 days after treatment

Gobbi F et al. Lancet Inf Dis 2017

Diagnosis: is a satisfactory test available for screening?

• Presence of eggs in stools or in urine

• Serology (type and cute‐off)

• Circulating antigens (CCA/CAA)

• Symptoms and eosinophilia

• PCR? Urines? Stools?

Table 3. Predictive values of a combination of positive ICT  (Se 96% Sp 79%, PPV 72%, NPV 97%) and a positive (PPV) or a negative (NPV) second test, 

according to Latent Class Analysis (prev=35%)

Beltrame A, Guerriero M, Angheben A, Gobbi F, Requena-Mendez A, et al. (2017) Accuracy of parasitological and immunological tests for the screening of human

schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis.

PLOS Neglected Tropical Diseases 11(6): e0005593

Diagnosis: is a satisfactory test available forscreening?

• In non‐endemic countries no existingguidelines/recommendations on management of (acute) and chronicschistosomiasis

40 mg/kg single dose,but…

Is an effective treatment available? Ok praziquantel…But how manydoses?

92 (62.2%) standard treatment

148 recordsincluded

56 (37.8%) differenttreatment

25

differentdosage

12

more than one 

day

13

repeateddose

1

more thanone day and repeated dose

2

repeated dose and different

dosage

3

more than one day and different

dosage

SYSTEMATIC REVIEW ON SCHISTOSOMIASIS TREATMENT IN NON‐ENDEMIC COUNTRIES 

Cucchetto G et al., 2018 (to be submitted)

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SYSTEMATIC REVIEW ON SCHISTOSOMIASIS TREATMENT IN NON‐ENDEMIC COUNTRIES 

Cucchetto G et al., 2018 (to be submitted)

We have a dream…

…A multi center RCT in non endemic countries toassess the efficacy of praziquantel

One dose vs multiple doses

To screen or not to screen? 

1. Important health problem

2. Natural history well understood

3. Detectable early stage

4. Early treatment more beneficial

5. Suitable test for early stage

6. Acceptable test

7. Adequate intervals determined

8. Adequate health services

9. Risks less than benefits

10. Balance cost/benefits Wilson & Junger criteria WHO 1968

To screen or not to screen? Balance cost/benefits?? Is presumptive treatment an option?  

PLoS Negl Trop Dis. 2016 Aug 10;10(8):e0004910. doi: 10.1371/journal.pntd.0004910. eCollection 2016 Aug.Economic Analysis of the Impact of Overseas and Domestic Treatment and Screening Options for IntestinalHelminth Infection among US-Bound Refugees from Asia.Maskery B1, Coleman MS1, Weinberg M1, Zhou W1, Rotz L1, Klosovsky A2, Cantey PT3, Fox LM3, Cetron MS1, Stauffer WM1,4.

Ivermectin: A Drug Worthy of a Nobel Prize, but Inaccessible for Those Who Need It22 October 2015

Conclusions and an unanswered last question

• Relevant health problems

• Screening recommended (e.g. new Italian MOH guidelines)

Is screening feasibleconsidering the currentpolitical mainstream in many countries?